A variety of radionuclides are known to be useful for radioimaging, including .sup.67 Ga, .sup.99m Tc (technetium-99m), .sup.111 In, .sup.123 I, .sup.125 I, .sup.169 Yb or .sup.186 Re. The use of chelating agents for radiolabeling large polypeptides such as proteins is known in the prior art. Methods for labeling peptides and polypeptides with technetium-99m have been disclosed in the prior art.
Byrne et al., U.S. Pat. No. 4,434,151 describe homocysteine thiolactone bifunctional chelating agents that can couple radionuclides to terminal amino-containing compounds capable of localizing in an organ or tissue to be imaged.
Fritzberg, U.S. Pat. No. 4,444,690 describes a series of technetium-chelating agents based on 2,3-bis(mercaptoacetamido)propanoate.
Gansow et al., U.S. Pat. No. 4,472,509 teach methods of manufacturing and purifying metal chelate-conjugated monoclonal antibodies.
Byrne et al., U.S. Pat. Nos. 4,571,430 and 4,575,556 describe novel homocysteine thiolactone bifunctional chelating agents for chelating radionuclides that can couple radionuclides to terminal amino-containing compounds capable of localizing in an organ or tissue to be imaged.
Nicolotti et al., U.S. Pat. No. 4,861,869 describe bifunctional coupling agents useful in forming conjugates with biological molecules such as antibodies. This reference describes compounds such as S-benzoylmercaptoacetylglycylglycylglycine.
European Patent Application No. 84109831.2 describes technetium chelating complexes of bisamido-bisthiol-ligands and salts thereof, used primarily as renal function monitoring agents.
European Patent Application No. 86100360.6 describes dithiol, diamino, or diamidocarboxylic acids or amine complexes useful for making technetium imaging agents.
European Patent Application No. 88104755.9 describes various S-protected mercaptoacetylglycylglycine chelating groups bound to large proteins such as antibodies.
Albert et al., UK Patent Application No. 8927255.3 disclose radioimaging using somatostatin derivatives such as octreotide labeled with .sup.111 In via a chelating group bound to the amino terminus.
Flanagan et al., European Patent Application No. 90306428.5 disclose technetium-99m labeling synthetic peptide fragments via a set of organic chelating molecules.
Albert et al., European Patent Application No. WO 91/01144 disclose radioimaging using radiolabeled peptides related to growth factors, hormones, interferons and cytokines and comprised of a specific recognition peptide covalently linked to a radionuclide chelating group.
Davison et al., Inorg. Chem. 20: 1629-1632 (1981) disclose oxotechnetium chelate complexes.
Fritzberg et al., J. Nucl. Med. 23: 592-598 (1982) disclose a technetium chelating agent based on N,N'-bis(mercaptoacetyl)-2,3-diaminopropanoate.
Byrne and Tolman, J. Nucl. Med. 24: P126 (1983) disclose a bifunctional thiolactone chelating agent for coupling technetium-99m to biological molecules.
Bryson et al., Inorg. Chem. 27: 2154-2161 (1988) describe thiolate ligands for complexing with technetium.
Bryson et al., Inorg. Chem. 29: 2948-2951 (1990) describe thiolate ligands for complexing with technetium.
Kwekkeboom et al., J. Nucl. Med. 32: 981 (1991) Abstract #305 relates to radiolabeling somatostatin analogues with .sup.111 In.
Albert et al., Abstract LM10, 12th American Peptide Symposium (1991) describe uses for .sup.111 In-labeled diethylenetriaminopentaacetic acid-derivatized somatostatin analogues.
Dean, co-pending U.S. patent application Ser. No. 07/653,012, now abandoned, teaches reagents and methods for preparing peptides comprising a technetium-99m chelating group having the general structure Cp(aa)Cp, wherein Cp is a protected cysteine and (aa) is an amino acid, the chelating group being covalently linked to a specific binding peptide for radioimaging in vivo, and is hereby incorporated by reference.
Reno and Bottino, European Patent Application No. 87300426.1 disclose radiolabeling antibodies with technetium-99m.
Bremer et al., EPC Application No. 87118142.6 disclose organ-specific radioimaging using technetium-99m radiolabeled proteins.
Pak et al., European Patent Application No. WO 88/07382 disclose a method for labeling antibodies with technetium-99m.
Goedemans et al., PCT Application No. WO 89/07456 describe radiolabeling proteins using cyclic thiol compounds, particularly on 2-iminothiolane and derivatives.
Schochat et al., PCT Application No. WO 89/09405 disclose direct radiolabeling of proteins comprised of at least one "pendent" sulfhydryl group.
Dean et al., PCT Application No. WO 89/12625 describe bifunctional coupling agents for technetium-99m labeling of proteins or peptides.
Thornback et al., EPC Application No. 90402206.8 describe preparation and use of radiolabeled proteins or peptides using thiol-containing compounds, particularly 2-iminothiolane.
Stuttle, PCT Application No. WO 90/15818 describes technetium-99m labeling of RGD-containing oligopeptides.
Rhodes, Sem. Nucl. Med. 4: 281-293 (1974) teaches the labeling of human serum albumin with technetium-99m.
Khaw et al., J. Nucl. Med. 23: 1011-1019 (1982) disclose methods for labeling biologically active macromolecules with technetium-99m.
Knight et al., Abstract #209, 37th Annual Meeting, Society for Nuclear Medicine (1990) describe thrombus imaging with technetium-99m labeled peptides.
Cox et al., Abstract, 7th International Symposium on Radiopharmacology, p. 16, 1991, disclose the use of .sup.131 I- and .sup.111 In-labeled somatostatin analogues in radiolocalization of endocrine tumors in vivo by scintigraphy.